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Carcinoma

Carcinoma, Squamous Cell

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Lymphoma, T-Cell

Lymphoma, T-Cell, Peripheral

Lymphoma, T-Cell, Cutaneous

Urinary Bladder Neoplasms

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Carcinoma, Renal Cell

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Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Skin Diseases

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Male Urogenital Diseases

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Nevus

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Female Urogenital Diseases

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Female Urogenital Diseases and Pregnancy Complications

Urologic Diseases

Lymphoma, Non-Hodgkin

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Endocrine System Diseases

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Renal Cell Carcinoma

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Neuroendocrine Tumor

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All Drugs and Chemicals

Antineoplastic Agents

Anti-Infective Agents

Antibodies

Durvalumab

Poly ICLC

Immunoglobulins

Tremelimumab

Antineoplastic Agents, Immunological

Interferons

Immunologic Factors

Subjects received durvalumab (1500 mg IV every 4 weeks \[Q4W\] for 12 cycles). Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (75 mg IV Q4W for the first 4 cycles).

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (10 mg) intratumorally on days 1, 8, and 15 of Cycle 1, days 1 and 15 of Cycle 2 and day 1 of Cycles 3 and 4.

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.

Poly-ICLC

Craig L Slingluff, Jr., MD

Nina Bhardwaj, MD, PhD

This is an open-label, multicenter, Phase 1/2 study of the CTLA-4 antibody, tremelimumab, and the PD-L1 antibody, durvalumab (MEDI4736), in combination with the tumor microenvironment (TME) modulator poly-ICLC, a TLR3 agonist, in subjects with advanced, measurable, biopsy-accessible cancers.

This is an open-label, multicenter, Phase 1/2 study of the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody, tremelimumab, and the programmed cell death ligand-1 (PD-L1) antibody, durvalumab (MEDI4736), in combination with the tumor microenvironment (TME) modulator poly-ICLC, a toll-like receptor 3 (TLR3) agonist, in subjects with advanced, measurable, biopsy-accessible cancers. Subjects will receive intratumoral and intramuscular (IM) administration of poly-ICLC and intravenous (IV) administration of durvalumab, together with either IV or intratumoral administration of tremelimumab. The study will be conducted in 2 phases.

Phase 1: There will be enrollment to 3 subject cohorts in Phase 1, with staggered initiation of enrollment.

* Cohort 1A: IV Durvalumab + Intratumoral/IM Poly-ICLC. After safety is demonstrated in the first 3-6 subjects in Cohort 1A, Cohorts 1B and 1C will open to enrollment.
* Cohort 1B: IV Durvalumab + IV Tremelimumab + Intratumoral/IM Poly-ICLC.
* Cohort 1C: IV Durvalumab + Intratumoral Tremelimumab + Intratumoral/IM Poly-ICLC.

Phase 2: Upon determination of the recommended combination dose in Cohort 1C, up to 66 evaluable subjects will be treated in Phase 2. Up to 6 subjects will be initially enrolled by tumor type (head and neck squamous cell carcinoma, locally recurrent or metastatic breast cancer, sarcoma, Merkel cell carcinoma, cutaneous T-cell lymphoma, melanoma after failure of available therapies, genitourinary cancers and solid tumors with accessible metastases). Subjects enrolled in Cohort 1C will be included in Phase 2 in the applicable tumor type. Data from all subjects in each Phase 2 tumor type will be reviewed for safety/efficacy to select up to 3 tumor types that demonstrate an efficacy signal, defined as at least 1 of 6 subjects within a tumor type who achieve a partial response (PR) or complete response (CR) by immune-related RECIST (irRECIST) or RECIST 1.1, or stable disease (SD) for at least 6 months. Up to 6 additional subjects in each of the selected tumor types may be enrolled in the expansion.

In Phase 1, Cohort 1A was opened first and after the safety of durvalumab and poly-ICLC was demonstrated, Cohorts 1B and 1C were open in parallel. In Phase 2, all tumor types were opened in parallel, and subjects included in Cohort 1C were included and reported in their respective tumor type in Phase 2.

A Study of Tremelimumab and IV Durvalumab Plus Poly-ICLC in Subjects With Biopsy-accessible Cancers

A Phase 1/2 Study of In Situ Vaccination With Tremelimumab and IV Durvalumab (MEDI4736) Plus the Toll-like Receptor Agonist Poly-ICLC in Subjects With Advanced, Measurable, Biopsy-accessible Cancers

Toxicity was graded in accordance with the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.03. Adverse events (AEs) were reported based on clinical laboratory tests, vital signs, physical examinations, and any other medically indicated assessments, including subject interviews, from the time informed consent was signed through 90 days after the last dose of study treatment. Treatment-emergent AEs were those that occurred or worsened after administration of the first dose of study treatment.

Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 21 days before the first dose of study treatment), and in Cycles 4, 7, 9 and 11, when a subject discontinued treatment prematurely and 28 days after the last dose of study treatment. Per irRECIST, measurable lesions were categorized as follows: Complete Response (irCR): Complete disappearance of all target lesions; Partial Response (irPR): ≥ 30% decrease from baseline in the Total Measured Tumor Burden (TMTB); Progressive Disease (irPD): ≥ 20% increase from nadir in Total Measured Tumor Burden (TMTB); Stable Disease (irSD): not meeting above criteria.

Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 21 days before the first dose of study treatment), and in Cycles 4, 7, 9 and 11, when a subject discontinued treatment prematurely and 28 days after the last dose of study treatment.

PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression according to irRECIST or to the date of death, if disease progression did not occur. Per irRECIST, Progressive Disease (irPD) was defined as a ≥ 20% increase from nadir in the Total Measured Tumor Burden (TMTB).

Tumor responses were evaluated using appropriate imaging and categorized according to irRECIST at Screening (up to 21 days before the first dose of study treatment), and in Cycles 4, 7, 9 and 11, when a subject discontinued treatment prematurely and 28 days after the last dose of study treatment. Per irRECIST, measurable lesions were categorized as follows: Complete Response (irCR): Complete disappearance of all target lesions; Partial Response (irPR): ≥ 30% decrease from baseline in the Total Measurable Tumor Burden (TMTB); Progressive Disease (irPD): ≥ 20% increase from nadir in Total Measured Tumor Burden (TMTB); Stable Disease (irSD): not meeting above criteria.

Overall Disease Control Rate was defined as the percentage of subjects who had irSD for at least 6 months, or irPR or irCR over a period of at least 4 weeks. Subjects who dropped out prior to meeting the responder criteria were considered non-responders.

Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 21 days before the first dose of study treatment), and in Cycles 4, 7, 9 and 11, when a subject discontinued treatment prematurely and 28 days after the last dose of study treatment. Per RECIST 1.1, target lesions are categorized as follows: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions or presence of new lesions; Stable Disease (SD): small changes that did not meet above criteria.

Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 21 days before the first dose of study treatment), and in Cycles 4, 7, 9 and 11, when a subject discontinued treatment prematurely and 28 days after the last dose of study treatment.

PFS was measured from the date of the first dose of study treatment to the date of earliest disease progression according to RECIST 1.1 or to the date of death, if disease progression did not occur. Per RECIST 1.1, Progressive disease (PD) was defined as a ≥ 20% increase in the sum of the longest diameter of target lesions or the presence of new lesions.

Tumor responses were evaluated using appropriate imaging and categorized according to RECIST 1.1 at Screening (up to 21 days before the first dose of study treatment), and in Cycles 4, 7, 9 and 11, when a subject discontinued treatment prematurely and 28 days after the last dose of study treatment. Per RECIST 1.1, target lesions are categorized as follows: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): ≥ 30% decrease in the sum of the longest diameter of target lesions; Progressive Disease (PD): ≥ 20% increase in the sum of the longest diameter of target lesions or presence of new lesions; Stable Disease (SD): small changes that did not meet above criteria.

Overall Disease Control Rate was defined as the percentage of subjects who had SD for at least 6 months, or PR or CR over a period of at least 4 weeks. Subjects who dropped out prior to meeting the responder criteria were considered non-responders.

After completion of treatment, all subjects were followed for survival every 3 months for 2 years after completion of treatment; then every 6 months until 5 years from study entry; then yearly until 10 years from study entry. OS was measured from the date of the first dose of study treatment to the date of death or last follow-up. Subjects lost to follow-up were censored on the date when they were last known to be alive. Per protocol amendment 6.0, all post study follow-up for the collection of survival data was discontinued as of February 28, 2022. The last collection of survival data was on February 23, 2022.

MedImmune LLC

Cancer Research Institute, New York City

Ludwig Institute for Cancer Research

AE documentation includes onset/resolution dates, severity using the NCI CTCAE (version 4.03), seriousness, relationship to study drug, study drug action taken, treatment, and outcome. In summaries, preferred terms are counted only once per subject at the maximum reported grade.

Subjects received durvalumab (1500 mg IV every 4 weeks \[Q4W\] for 12 cycles). Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.

Durvalumab

Poly-ICLC

Phase 1, Cohort 1A

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (75 mg IV Q4W for the first 4 cycles).

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.

Durvalumab

Tremelimumab

Poly-ICLC

Phase 1, Cohort 1B

Subjects received durvalumab (1500 mg IV Q4W for 12 cycles) and tremelimumab (10 mg) intratumorally on days 1, 8, and 15 of Cycle 1, days 1 and 15 of Cycle 2 and day 1 of Cycles 3 and 4.

Poly-ICLC (1 mg) was administered intratumorally on days 1, 3, 5, 8, 10 and 15 and intramuscularly on days 17, 22, and 24 of Cycle 1 as well as intramuscularly on days 1, 3, 8, 10, 15, 17, 22 and 24 of Cycle 2 and on days 1 and 4 of Cycle 3.

Durvalumab

Tremelimumab

Poly-ICLC

Cohort 1C + Phase 2; Head + Neck Squamous Cell Carcinoma

Cohort 1C + Phase 2; Locally Recurrent or Metastatic Breast Cancer

Cohort 1C + Phase 2; Sarcoma

Cohort 1C + Phase 2; Merkel Cell Carcinoma

Cohort 1C + Phase 2; Melanoma After Failure of Available Therapies

Cohort 1C + Phase 2; Genitourinary Cancers With Accessible Metastases

Cohort 1C + Phase 2; Solid Tumors With Accessible Masses

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

PS 0 = Fully active, able to carry on all pre-disease performance without restriction; PS 1 = Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work; PS 2 = Ambulatory and capable of all selfcare but unable to carry out any work activities; up and about more than 50% of waking hours; PS 3 = Capable of only limited selfcare; confined to bed or chair more than 50% of waking hours; PS 4 = Completely disabled; cannot carry on any selfcare; totally confined to bed or chair; PS 5 = Dead

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

All subjects who received at least one dose of study medication.

Jonathan Skipper

Number of Subjects with TEAEs

Number of Subjects with Treatment-Related TEAEs (TRAEs)

Number of Subjects with Serious TRAEs

Number of Subjects with Dose-Limiting Toxicities (DLTs)

Number of Subjects who Died on Study

All subjects who received at least one dose of study treatment.

Number of Subjects With Treatment-emergent Adverse Events (TEAEs)

All subjects who had at least one dose of study medication and one baseline and at least one post-baseline disease assessment.

Number of Subjects With Best Overall Tumor Response by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)

All subjects who had at least one dose of study medication.

Median Progression-free Survival (PFS) by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) as Estimated Using the Kaplan-Meier Method

Overall Disease Control Rate as Measured by Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST)

Number of Subjects With Best Overall Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Median PFS by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as Estimated Using the Kaplan-Meier Method

Overall Disease Control Rate as Measured by Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

All subjects that had at least one study treatment.

Median Overall Survival (OS) as Estimated Using the Kaplan-Meier Method

Overall Study

Carcinoma, Ductal

Carcinoma in Situ

Carcinoma, Intraductal, Noninfiltrating

Breast Carcinoma In Situ

Vaccines

Hormones

Exemestane

Letrozole

Anastrozole

Aromatase Inhibitors

polysaccharide-K

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormone Antagonists

Antineoplastic Agents, Hormonal

MUC1 peptide vaccine with poly-ICLC adjuvant Hiltonol administered subcutaneously (SQ) Anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg by mouth daily

Anastrozole 1 mg, letrozole 2.5 mg, or exemestane 25 mg by mouth daily

MUC1, a therapeutic vaccine, is a transmembrane glycoprotein and a member of the mucin family of molecules.

MUC1 Peptide Vaccine

A synthetic dsRNA viral mimic and host-defense activator, mimics nature by combining the essential elements of human immunity.

Hiltonol®

A type of hormone therapy for cancer used to inhibit aromatase to treat a hormone-related breast cancer.

Aromatase Inhibitor

Kelsey Mitch, RN, BSN

Lucia Borrasso, BS

Emilia Diego, MD

Post-menopausal women with biopsy-proven DCIS will be enrolled into two cohorts. One cohort will receive neoadjuvant therapy with an aromatase inhibitor alone for about 12 weeks prior to surgery at 12 weeks. The second cohort will receive neoadjuvant therapy with an aromatase inhibitor and MUC1 vaccination (MUC1 peptide + Hiltonol®) pre-operatively at baseline, and weeks 2 and 10, followed by surgery at about 12 weeks. Patients in the vaccine cohort will be offered an optional boost vaccine 6 months after surgery.

DCIS is frequently detected by screening mammography, and may develop into invasive disease. However, not all DCIS will progress to invasive breast cancer, and some patients are overtreated. Vaccines for DCIS might facilitate therapeutic de-escalation, and allow less aggressive therapy. The TAA MUC1 is expressed in DCIS, and vaccines specific for MUC1 are safe and decrease the rate of recurrence of high-risk premalignant lesions in colon cancer. This clinical trial is designed to evaluate mechanisms of immune activation and suppression in patients with DCIS, both within the peripheral blood and within the DCIS lesion, and will provide data to guide the development of larger trials to evaluate the impact of a MUC1 vaccine to prevent disease recurrence. Ultimately, vaccine success in intercepting the development of breast cancer will provide critical data for the application of these strategies in breast cancer prevention in high-risk individuals.

Prototype DAA/TAA Vaccine Targeting MUC1 for Immune Interception and Prevention in Ductal Carcinoma In Situ

A Clinical Study of a Prototype DAA/TAA Vaccine Targeting MUC1 for Immune Interception and Prevention in Ductal Carcinoma In Situ

Percentage of patients with a 2-fold or greater increase in serum anti-MUC1 IgG from screening date. Serum IgG is measured using enzyme-linked immunosorbent assay (ELISA).

Number of AEs and SAEs related to study treatment using Common Terminology Criteria for Adverse Events version 5 (CTCAE v.5).

Percentage of patients who experience a greater than 4-week variation in the time to planned surgery that is related to study participation.

A Glimmer of Hope Foundation

Breast Cancer Research Foundation

Finn, Olivera, PhD

Associate Professor of Surgery

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of Tremelimumab and IV Durvalumab Plus Poly-ICLC in Subjects With Biopsy-accessible Cancers	NCT02643303	Head and Neck S... Breast Cancer Sarcoma Merkel Cell Car... Cutaneous T-Cel... Melanoma Renal Cancer Bladder Cancer Prostate Cancer Testicular Canc... Solid Tumor	Durvalumab Tremelimumab Poly-ICLC	18 Years -	Ludwig Institute for Cancer Research
Prototype DAA/TAA Vaccine Targeting MUC1 for Immune Interception and Prevention in Ductal Carcinoma In Situ	NCT06218303	Ductal Carcinom...	MUC1 Peptide Va... Hiltonol® Aromatase Inhib...	18 Years -	University of Pittsburgh
Prototype DAA/TAA Vaccine Targeting MUC1 for Immune Interception and Prevention in Ductal Carcinoma In Situ	NCT06218303	Ductal Carcinom...	MUC1 Peptide Va... Hiltonol® Aromatase Inhib...	18 Years -	University of Pittsburgh
A Study of Tremelimumab and IV Durvalumab Plus Poly-ICLC in Subjects With Biopsy-accessible Cancers	NCT02643303	Head and Neck S... Breast Cancer Sarcoma Merkel Cell Car... Cutaneous T-Cel... Melanoma Renal Cancer Bladder Cancer Prostate Cancer Testicular Canc... Solid Tumor	Durvalumab Tremelimumab Poly-ICLC	18 Years -	Ludwig Institute for Cancer Research

Spots Global Cancer Trial Database for hiltonol®

Every month we try and update this database with for hiltonol® cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for hiltonol®

Every month we try and update this database with for hiltonol® cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for hiltonol® cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.